dbSNP rs557051546: NTMT2:p.Val161Asp (chr1-170166653-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136107.2(NTMT2):c.482T>A(p.Val161Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NTMT2
NM_001136107.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.432

Publications

0 publications found

Variant links:

Genes affected

NTMT2 (HGNC:31932): (N-terminal Xaa-Pro-Lys N-methyltransferase 2) Enables N-terminal protein N-methyltransferase activity. Involved in N-terminal protein amino acid methylation. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NTMT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029197007).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136107.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTMT2	NM_001136107.2	MANE Select	c.482T>A	p.Val161Asp	missense	Exon 3 of 4	NP_001129579.1	Q5VVY1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NTMT2	ENST00000439373.3	TSL:1 MANE Select	c.482T>A	p.Val161Asp	missense	Exon 3 of 4	ENSP00000408058.3	Q5VVY1
NTMT2	ENST00000962802.1		c.482T>A	p.Val161Asp	missense	Exon 3 of 4	ENSP00000632861.1
NTMT2	ENST00000367764.3	TSL:5	n.540T>A		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000632

AC:

AN:

158218

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1399888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35740

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079068

Other (OTH)

AF:

0.00

AC:

AN:

58154

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.4

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0013

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.70

M_CAP

Benign

0.0051

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.1

PhyloP100

0.43

PrimateAI

Benign

0.29

PROVEAN

Benign

2.9

REVEL

Benign

0.046

Sift

Benign

0.62

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.15

MutPred

0.44

Gain of disorder (P = 0.0052)

MVP

0.13

ClinPred

0.054

GERP RS

0.18

Varity_R

0.46

gMVP

0.42

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over